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CHAPTER 18
MICROBIAL MODELS: THE GENETICS OF
VIRUSES AND BACTERIA
Genetics of Viruses
• Virus: parasitic infective agent that can not
survive outside a host.
• Viruses take over the host in order to replicate
and produce what it needs to survive.
• Classification of viruses is based on:
– Genetic material: DNA, RNA, Protein…
– Capsid type(protein shell surrounding the genetic
material
– Presence or absence of viral envelope
– Type of cell the virus infects (Host cell type)
Virus: genome enclosed in a
protective coat
• Viruses: crystallized was odd since not even
the simplest cells can aggregate into regular
crystals.
• But, viruses are not cells.
– They are infectious particles consisting of nucleic
acid encased in a protein coat, and, in some
cases, a membranous envelope.
– Viruses range in size from only 20nm in diameter
to that barely resolvable with a light microscope.
– DNA or RNA; single or double strand
• 4 genes to several hundred
• The capsid is a protein shell enclosing the viral
genome.
• Capsids are build of a large
number of protein subunits
called capsomeres, but
with limited diversity.
– The capsid of the tobacco
mosaic virus has over 1,000
copies of the same protein.
– Adenoviruses have 252
identical proteins arranged
into a polyhedral capsid as an icosahedron.
• Some viruses have
viral envelopes,
membranes cloaking
their capsids.
• These envelopes are
derived from the
membrane of the host
cell.
• They also have some
viral proteins and
glycoproteins.
• The most complex
capsids are found in
viruses that infect
bacteria, called
bacteriophages or
phages.
• The T-even phages
that infect Escherichia
coli have a 20-sided
capsid head that
encloses their DNA and
protein tail piece that
attaches the phage to
the host and injects the
phage DNA inside.
Virus Reproduction
• Viruses are obligate intracellular parasites.
• They can reproduce only within a host cell.
• An isolated virus is unable to reproduce - or
do anything else, except infect an appropriate
host.
• Viruses lack the enzymes for metabolism or
ribosomes for protein synthesis.
• An isolated virus is merely a packaged set
of genes in transit from one host cell to
another.
• Some viruses (like the rabies virus) have a
broad enough host range to infect several
species, while others infect only a single
species.
• Most viruses of eukaryotes attack specific
tissues.
– Human cold viruses infect only the cells lining the
upper respiratory tract.
– The AIDS virus binds only to certain white blood
cells.
• A viral infection begins when
the genome of the virus
enters the host cell.
• Once inside, the viral genome
commandeers its host,
reprogramming the cell to
copy viral nucleic acid and
manufacture proteins from
the viral genome.
• The nucleic acid molecules
and capsomeres then selfassemble into viral particles
and exit the cell.
4. Phages reproduce using
lytic or lysogenic cycles
Lytic Cycle culminates in the death of the host cell
Lysigenic does not destroy the host cell.
• While phages have the potential to wipe out a
bacterial colony in just hours, bacteria have
defenses against phages.
– Natural selection favors bacterial mutants with
receptors sites that are no longer recognized by a
particular type of phage.
– Bacteria produce restriction nucleases that
recognize and cut up foreign DNA, including
certain phage DNA.
• Modifications to the bacteria’s own DNA prevent its
destruction by restriction nucleases.
– But, natural selection favors resistant phage
mutants.
• In the lysogenic cycle, the phage genome
replicates without destroying the host cell.
• Temperate phages, like phage lambda, use
both lytic and lysogenic cycles.
• Within the host, the virus’ circular DNA
engages in either the lytic or lysogenic cycle.
• During a lytic cycle, the viral genes
immediately turn the host cell into a virusproducing factory, and the cell soon lyses and
releases its viral products.
The lambda phage which infects E. coli
demonstrates the cycles of a temperate phage.
Viruses equipped with an outer envelope use the
envelope to enter the host cell.
• These enveloped
viruses do not
necessarily kill
the host cell.
Herpesvirus
• Some viruses have envelopes that are not
derived from plasma membrane.
– The envelope of the herpesvirus is derived from the
nuclear envelope of the host.
– These double-stranded DNA viruses reproduce within
the cell nucleus using viral and cellular enzymes to
replicate and transcribe their DNA.
– Herpesvirus DNA may become integrated into the cell’s
genome as a provirus.
– The provirus remains latent within the nucleus until
triggered by physical or emotional stress to leave the
genome and initiate active viral production.
Class IV:single strand RNA
Class V: RNA as genome to make RNA
• Class VI: Retroviruses have the most
complicated life cycles.
– These carry an enzyme, reverse transcriptase,
which transcribes DNA from an RNA template.
– The newly made DNA is inserted as a provirus into
a chromosome in the animal cell.
– The host’s RNA polymerase transcribes the viral
DNA into more RNA molecules.
• These can function both as mRNA for the synthesis of viral
proteins and as genomes for new virus particles released
from the cell.
• Human immunodeficiency
virus (HIV), the virus that
causes AIDS (acquired
immunodeficiency
syndrome) is a retrovirus.
• The viral particle includes
an envelope with glycoproteins for binding to
specific types of blood
cells, a capsid containing
two identical RNA strands
as its genome and two
copies of reverse
transcriptase.
Defenses against disease
• Modern medicine has developed vaccines, harmless
variants or derivatives of pathogenic microbes, that
stimulate the immune system to mount defenses against
the actual pathogen.
• The first vaccine: late 1700s by E Jenner to fight smallpox.
– Jenner learned from his patients that milkmaids who
had contracted cowpox, a milder disease that usually
infects cows, were resistant to smallpox.
– In his famous experiment in 1796, Jenner infected a
farmboy with cowpox, acquired from the sore of a
milkmaid with the disease.
– When exposed to smallpox, the boy resisted the
disease.
– Because of their similarities, vaccination with the
cowpox virus sensitizes the immune system
Antibiotics & Viruses
• Antibiotics don’t work
• Some recently-developed drugs do
combat some viruses, mostly by
interfering with viral nucleic acid
synthesis.
– AZT interferes with reverse transcriptase of
HIV.
– Acyclovir inhibits herpes virus DNA
synthesis
Emergent Viruses
• Several very dangerous
“emergent viruses” have
risen to prominence.
– HIV, the AIDS virus,
seemed to appear suddenly
in the early 1980s.
– Each year new strains of
influenza virus; deaths are
not uncommon.
– The deadly Ebola
virus has caused
hemorrhagic fevers
in central Africa
periodically since
1976.
• Emerge by three processes:
– Mutation of existing viruses is a major source of
new viral diseases.
• RNA viruses tend to have high mutation rates
because replication of their nucleic acid lacks
proofreading.
• Some mutations create new viral strains with
sufficient genetic differences from earlier
strains that they can infect individuals who
had acquired immunity to these earlier
strains.
– This is the case in flu epidemics.
• Another source of new viral diseases is the
spread of existing viruses from one host
• About three-quarters of new human diseases
have may have originated in other animals.
– Hantavirus, which killed dozens of people in 1993,
normally infects rodents, especially deer mice.
• That year unusually wet weather in the southwestern
U.S. increased the mice’s food,
exploding its populations.
• Humans acquired hantavirus
when they inhaled dust
containing traces of urine
and feces from infected mice.
• Finally, a viral disease can spread from a
small, isolated population to a widespread
epidemic.
– AIDS went unnamed and virtually unnoticed for
decades before spreading around the world.
– Technological and social factors, including
affordable international travel, blood transfusion
technology, sexual promiscuity, and the abuse of
intravenous drugs, allowed a previously rare
disease to become a global scourge.
• These emerging viruses are generally not
new but are existing viruses that expand their
host territory.
• Environmental change can increase the viral
traffic responsible for emerging disease.
Viruses & Cancer
• Peyton Rous discovered that a virus causes cancer
in chickens; scientists have recognized that other
viruses cause animal cancers
• Tumor viruses include retrovirus, papovavirus,
adenovirus, and herpesvirus types
• The hepatitis B virus is associated with liver cancer.
• The Epstein-Barr virus, which causes infectious
mononucleosis, has been linked to several types of
cancer in parts of Africa, notably Burkitt’s lymphoma.
• Papilloma viruses are associated with cervical
cancers.
• The HTLV-1 retrovirus causes a type of adult
leukemia.
• All tumor viruses transform cells into cancer
cells after integration of viral nucleic acid into
host DNA.
– Viruses may carry oncogenes that trigger
cancerous characteristics in cells.
• These oncogenes are often versions of proto-oncogenes
that influence the cell cycle in normal cells.
• Proto-oncogenes generally code for growth factors or
proteins involved in growth factor function.
– In other cases, a tumor virus transforms a cell by
turning on or increasing the expression of protooncogenes.
• It is likely that most tumor viruses cause
cancer only in combination with other
mutagenic events.
Plant Viruses
• In horizontal transmission, a plant is infected
with the virus by an external source.
– Plants are more susceptible if their protective
epidermis is damaged, perhaps by wind, chilling,
injury, or insects.
– Insects are often carriers of viruses, transmitting
disease from plant to plant.
• In vertical transmission, a plant inherits a viral
infection from a parent.
– This may occurs by asexual propagation or in
sexual reproduction via infected seeds.
Viroids and prions: infectious agents
simpler than viruses
• Viroids, smaller and simpler than even
viruses, consist of tiny molecules of naked
circular RNA that infect plants.
• Their several hundred nucleotides do not
encode for proteins but can be replicated by
the host’s cellular enzymes.
• These RNA molecules can disrupt plant
metabolism and stunt plant growth, perhaps
by causing errors in the regulatory systems
that control plant growth.
Viroids and prions: infectious agents
simpler than viruses
• Prions are infectious proteins that spread a disease.
– They appear to cause several degenerative brain
diseases including scrapie in sheep, “mad cow
disease”, and Creutzfeldt-Jacob disease in humans.
• According to the leading hypothesis, a prion is a misfolded
form of a normal brain protein.
• It can then convert a normal protein into the prion version,
creating a chain reaction that increases their numbers.
Virus Evolution
• Because viruses depend on cells for their own
propagation, it is reasonable to assume that they
evolved after the first cells appeared.
• Most molecular biologists favor the hypothesis that
viruses originated from fragments of cellular nucleic
acids that could move from one cell to another.
– A viral genome usually has more in common
with the genome of its host than with those of
viruses infecting other hosts.
– Perhaps the earliest viruses were naked bits of
nucleic acids that passed between cells via
injured cell surfaces